Stiff Man Syndrome: Science and experience

Stiff Man Syndrome was the name assigned to the condition of ‘progressive fluctuating muscular rigidity and spasm’ when first identified by Moersch and Woltman (1956). Classical SMS is associated with a number of other autoimmune diseases (Meinck and Thompson, 2002).

The condition is rare: during a 10-year period, 20 individuals were identified from a German population estimated to number between 2 and 3 million (Meinck and Thompson, 2002). The literature states that the average age of onset is in the third to fifth decade of life and in the majority of cases, SMS has an insidious onset with a slow progression over months or even years (Meinck and Thompson, 2002). There is no clear racial or ethnic predisposition (The Offical UK Stiff Man Syndrome Support Group and Charity, 2006), although the syndrome appears to be more common in women than men (Murinson, 2004).

Fluctuating stiffness and paroxysmal spasms of the trunk and legs are the primary features of SMS and its variants. The parts of the body affected include the face, neck, abdomen and/or arms, but more typically the legs or lumbar spine. Some individuals have reported to the author transient stiffness of one or both legs, sudden unexplained falls or failure of gait initiation that tends to manifest during emotional stress. Stiffness can be extremely painful and fluctuates from virtually absent to absolutely incapacitating. Body parts involved become rigidly immobile and often show skeletal abnormalities such as hyperlordosis (extreme lordsosis, where there is an increase in the normal anterior concavity of the lumbar spine) and ankylosis. Occasional fixed deformities of either the hands or feet can be present, as can other symptoms that can – albeit more rarely – affect speech, bladder and bowel function (Meinck and Thompson, 2002).

Spasms can occur spontaneously or be precipitated by a variety of stimuli such as noise or touch and may manifest as an excessive startle reaction (Meinck and Thompson, 2002). Spasms may also be precipitated by simple attempts to move. Emotional upsets, stress and minor motor demands or brisk movements are highly effective at provoking spasms. Excessive startle, space phobia, and spasms – often induced by emotional upset – probably contribute to the initial misdiagnosis of hysteria or depression in many patients (Meinck and Thompson, 2002; Murinson, 2004). After such symptoms are identified by the individual and consultant physician together, the author believes that specialist nurses can potentially contribute to the speeding up of investigations and diagnosis by being aware of the signs of SMS by helping individuals in describing their symptoms. In the author’s experience it is likely the individual will have very little idea about what is happening to their body and may require help in exploring their reaction to the condition.

In the author’s opinion, it is vital for specialist nurses to play their part in identifying people who may be suffering from SMS. It is sad but true that despite the severity of the syndrome, because it is rare, there is very little experience and knowledge of SMS in any group of healthcare specialists. This results in the condition not being recognised simply because it may seem like the person has depression or anxiety. Specialist nurses can act as an early warning system and a signpost for consultants. The key is watching for the tell-tale signs described here and making sure any suspicions are followed through with the appropriate tests to determine a diagnosis.

Reasonably common, co-existing conditions include thyroid disease, vitiligo and pernicious anaemia (Meinck and Thompson, 2002). However, the most common is type 1 diabetes, occurring in approximately 30% of people with SMS (Meinck and Thompson, 2002). Both type 1 diabetes and SMS feature immune responses to a particular enzyme: glutamic acid decarboxylase (GAD; Meinck and Thompson, 2002; Piquer et al, 2005; Raju et al, 2005).

GAD
Everyone has GAD but in the presence of specific antibodies the enzyme can be destroyed. In type 1 diabetes the destruction of GAD affects the transmission of insulin between the pancreas and the liver. In SMS, the destruction of GAD affects the transmission of nerve impulses, causing rigidity and painful spasms.

GAD is an enzyme commonly found in animals and is necessary for the synthesis of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA; Abe et al, 2005). GABA is the most important and abundant inhibitory neurotransmitter in the brain. While the GAD pathway is not the only source of GABA for the central nervous system, it is a significant source and interference of this pathway – such as when GAD is depleted by the presence of antibodies – can lead to rapid GABA depletion (Vianello et al, 2002; Abe et al, 2005). GABA serves as a natural anti-anxiety compound and as such the most potent anti-anxiety medications are based on augmenting the GABA-A receptor (Cheng and Chiou, 2006). A significant percentage of people with SMS have antibodies to GAD (Lohmann et al, 2003; Raju et al, 2005) and as a consequence these people also have elevated anxiety levels, which worsens the symptoms.

Results to date suggest that in both type 1 diabetes and SMS, antibodies to GAD can be detected. In both conditions, ß-cells can become activated and lead to the production of antibodies against GAD (Espay and Chen, 2006). The region of the GAD molecule targeted by these antibodies seems to differ between people with diabetes and those with SMS (Piquer et al, 2005; Lohmann et al, 2003). The differences between antibodies in both type 1 diabetes and SMS have been considered and research studies have been determining whether those patients with SMS and type 1 diabetes show a different response, human leukocyte antigen profile or clinical features from SMS individuals without type 1 diabetes (Raju et al, 2005). Further investigation into these features could lead to immunomodulatory therapy in both conditions.

Investigation
Because of the rarity and lack of awareness of SMS, reaching a diagnosis can be prolonged and very frustrating for the individual. Thus, it is essential that the following investigations are carried out if SMS is suspected (Meinck and Thompson, 2002).

• Blood tests to look for antibodies to GAD.
• Electromyelogram to measure nerve conduction in affected muscles.
• Magnetic resonance imaging or computed tomography scanning.
• Electroencephalogram to exclude epilepsy.

Central to evaluation for SMS is a detailed history and neurological examination. Hyper-reflexia (overactive or over-responsive reflexes) may be the only pathological finding during a neurological examination (Meinck and Thompson, 2002). The cardinal symptoms are essential to the diagnosis of this condition and isolated laboratory results do not stand alone. A related disorder has been found in association with lung or breast cancer and is distinguished by the production of anti-amphiphysin antibodies (Murinson, 2004).

Treatment
The response to medication is important in discriminating other causes of stiffness (Meinck and Thompson, 2002). The first-line medications are diazepam, a benzodiazepine that acts on neurotransmitters and helps in the treatment of anxiety and muscle spasms (Meinck and Thompson, 2002) and baclofen, which is also a muscle relaxant (The Official UK Stiff Man Syndrome Support Group and Charity, 2006). Second-line treatments include tizanidene and gabapentin. The above medications all have a sedating effect. Intravenous immunoglobulin has been shown to decrease the concentration of GAD antibodies and reduce SMS symptoms, with the added benefit of not acting as a sedative (Dalakas, 2005). All of these treatments are, in some respect, ‘hit and miss’ – it is as much a matter of correct titration of the dosage as changing medications in order to obtain the required effect, all of which takes time.

No treatment yet leads to a cure. However, medications are able to help control symptoms in the majority of cases. This is particularly true in classical SMS, which, if identified and managed appropriately, does not prevent a good outlook for the individual. It tends to be more difficult to control symptoms in the variant stiff limb syndrome due to progressive encephalomyelitis with rigidity.

Conclusion
Raising awareness of SMS is of great importance, as is a knowledge and understanding of SMS by nurses who are, in most instances, best placed to spot the symptoms and report them to consultant physicians to speed up the diagnostic process.